Kate Johnson

April 24, 2013

GENEVA, Switzerland — In patients with anal canal cancer, a brachytherapy boost after radiotherapy or chemoradiotherapy leads to high local control rates with acceptable toxicity, according to a new study.

This is the "fourth largest population of anal cancer patients treated with brachytherapy boost, with the longest follow-up evaluated in the literature," said Laetitia Lestrade, MD, from the Radiation Oncology Department at the Centre Léon Bérard in Lyon, France.

"We have confirmed the long-term local efficacy of brachytherapy boost with acceptable acute and late toxicity," she reported here at the 2nd European Society for Radiotherapy & Oncology Forum.

Local efficacy of the brachytherapy boost was also a strong prognostic factor for overall cancer-specific and colostomy-free survival, she added.

Retrospective Analysis From Single Center

Dr. Lestrade presented results from a retrospective analysis of 209 patients (median age, 65 years) with a histologic diagnosis of anal cancer who were treated at a single institution from 1992 to 2009. Treatment consisted with external-beam radiotherapy alone (n = 58) or in combination with chemotherapy (n = 151), and median follow-up was 73 months.

"Clinical examination with endorectal digital examination and, more recently, endorectal ultrasonography and magnetic resonance imaging for staging revealed that 80% had a diagnosis of squamous cell carcinoma, almost 30% had positive nodal status, and 30% had locally advanced disease," said Dr. Lestrade.

After a median interval of 32 days from initial radiotherapy, patients underwent a low-dose rate brachytherapy boost (72.2%) or a pulsed-dose rate brachytherapy boost (27.8%).

The median brachytherapy dose was 18 Gy; the median dose of radiotherapy and brachytherapy boost totaled 63 Gy, she said.

The primary end points of the study were local control and acute and late toxicity; secondary end points were overall survival, cancer-specific survival, colostomy-free survival, nodal-disease-free survival, and metastasis-free survival.

Five-year local control rates were 78.6% and 10-year local control rates were 73.9%. Grade 3/4 acute toxicity rates were 11.2% and late toxicity rates were 6.3%.

"Globally, the treatment was well tolerated," Dr. Lestrade noted.

Of the 44 patients (21%) who underwent colostomy, 6 experienced grade 3/4 anorectal late toxicity.

Specifically, 4.6% of patients experienced grade 3 chemotherapy-related acute toxicities, consisting of neutropenia (n = 1), renal toxicity (n = 4), cardiac toxicity (n = 1), and gastrointestinal toxicity (n = 1).

"Sphincter function, assessed with the WOMAC scale, was normal in 81.8% of patients, indicating normal continence to gas and stool," she said.

Overall survival was similar to that previously reported in the literature, she added.

Table. Survival After Brachytherapy Boost to Treatment for Anal Cancer

Survival End Point 5-Year Rate, % 10-Year Rate %
Overall 80.9 65.7
Cancer-specific 85.7 81.0
Colostomy-free 79.4 75.6
Nodal disease-free 82.1 78.5
Metastasis-free 90.5 88.8

 

On multivariate analysis, local control statistically influenced overall survival (P < .0001) and cancer-specific survival (P < .0001), as did concomitant chemotherapy (P = .048 and = .029, respectively).

Although brachytherapy is supported in international guidelines as a means of delivering a boost dose (54 to 59 Gy) to the tumor bed, its role has not been well evaluated in large cohorts, said Dr. Lestrade.

"A good response after radiotherapy with or without chemotherapy is probably a major criterion" for a higher possibility of success and better tolerance with brachytherapy, she said. "It should be a new selection criteria in daily clinical practice and an important stratification factor in designing prospective trials."

"This interesting study shows high local control and anal sphincter preservation rates with acceptable toxicity. The findings of this retrospective review highlight the role of brachytherapy in the multidisciplinary management of anal carcinoma," said José Luis López Guerra, MD, PhD, from the Hospital Universitario Virgen del Rocío in Seville, Spain.

Dr. Lopez Guerra has published a 20-year follow-up of anal cancer brachytherapy (Clin Transl Oncol. 2011;13:472-479), and was approached by Medscape Medical News for comment.

"These results are similar to our own findings in terms of preservation of the anal sphincter (79% and 84%, respectively) and severe late toxicity (approximately 10% in both studies). In addition, both studies observed high rates of 5-year local control (above 77%)," he said.

 
The management of anal cancer has undergone an interesting transformation over the last decades. Dr. Lopez Guerra
 

"The management of anal cancer has undergone an interesting transformation over the last decades. Prior to this period, the standard definitive treatment for carcinoma of the anal canal was abdominoperineal resection, which necessitated a permanent colostomy," Dr. Lopez Guerra told Medscape Medical News.

"The combination of external-beam radiotherapy to the pelvis (including primary tumor) and interstitial brachytherapy not only dramatically reduces the need for colostomy (only 21% of patients in the Lestrade study underwent colostomy), but also limits the volume of irradiated normal tissue, thereby decreasing late toxicity (only 6% in the Lestrade study), because brachytherapy is the most conformal treatment available to boost a small volume," he noted.

Dr. Lestrade and Dr. Lopez Guerra have disclosed no relevant financial relationships.

2nd European Society for Radiotherapy & Oncology (ESTRO) Forum: Abstract OC-0364. Presented April 21, 2013.

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